P811: A SINGLE CENTER HISTORICAL CONTROL STUDY OF ELTROMBOPAG ADDED TO IMMUNOSUPPRESSIVE THERAPY FOR SEVERE APLASTIC ANEMIA IN CHILDREN
Authors: B. yang, L. fu, H. li, H. chen, J. ma
Journal: HemaSphere (2022)

Background: Severe aplastic anemia is caused by immune-mediated destruction of bone marrow. Standard immunosuppressive therapy (rabbit anti-thymocyte globulin combined with cyclosporine) is effective, but the effect needs to be improved. A thrombopoietin-receptor agonist, eltrombopag, added to standard immunosuppressive therapy led to clinically significant increases in blood counts. We combined eltrombopag and standard immunosuppressive therapy in pediatric severe aplastic anemia patients. Aims: To evaluate the efficacy and safety of eltrombopag added to immunosuppressive therapy for severe aplastic anemia in children. Methods: The clinical data of patients with severe aplastic anemia and received immunosuppressive therapy from March 2013 to July 2020 were collected and analyzed retrospectively. We conducted a historical control study, in which the patients treated alone with immunosuppressive therapy were used as the control group. We compared the cases between control group and eltrombopag group, included hematological response, effective time, relapse, clonal evolution, adverse reactions, event free survival (EFS) and overall survival (OS). Results: 1. A total of 115patients (60 males), median aged 5.77 years, median follow-up time was 45 months, were enrolled in this study. All patients were diagnosed with severe or very severe aplastic anemia, including 49 patients in the historical control group and 66 patients in the eltrombopag group. 2. The complete response rate (CRR) at 3 months was 49.0% in eltrombopag cohort and 8.2% in historical control. The overall response rate (ORR) at 3months was 63.6% and 30.3% respectively. The CRR at 6 months was 50.0% in eltrombopag cohort and 10.2% in control cohort. The ORR at 6months were 71.2% and 57.1% respectively. There were significant differences of the CRR between two groups, there was no significant difference between two groups.3. The median effective time of the control group and eltrombopag group was 90 days and 71 days respectively (P = 0.007), the median complete remission time was 360 days and 98 days respectively (P < 0.001). The median time of separated from granulocyte colony stimulating factor (G-CSF), Red Blood Cell transfusion and Platelet transfusion in the control group were 105 days, 46 days and 54 days respectively, and 68 days, 45 days and 45 days in the eltrombopag group. There were significant differences in the time of separated from G-CSF (P = 0.003), Red Blood Cell transfusion (P = 0.001) and Platelet transfusion (P < 0.001) in the two groups. 4.The relapse rate was 4.1% (n = 2) in the control group and 10.2% (n = 5) in the eltrombopag group. One patient (2.0%) in the control group developed clonal evolution and progressed to myelodysplastic syndrome.5. The common adverse reaction were transient and reversible hyperbilirubinemia (13.6%, n = 9), elevated liver enzymes (4.5%, n = 3) and hyperuricemia (1.5%, n = 1).6. The 1-year OS and 2-year or of the control group was 100% and 98.5% respectively, comparing to 95.9% and 97.0% in eltrombopag group. The 2-year EFS of the control group and the eltrombopag group was 79.6% and 74.2%, respectively, and the 3-year EFS were 73.5% and 72.7%, respectively. Summary/Conclusion: The addition of eltrombopag to standard immunosuppressive therapy was associated with markedly higher rates and effected more quickly of hematologic response among pediatric severe aplastic anemia patients than in a historical cohort and showed a reliable security.